It has been known for over 150 years that bone responds to mechanical loading. Although the effects of exercise and mechanical loading on the musculoskeletal systems have been well documented, the actual mechanisms by which mechanical loading acts at the cellular level in the maintenance of skeletal integrity are not completely understood. Although greater attention is being given to exercise and nutrition as a means of preventing and/or treating osteoporosis, the regulatory mechanisms that control skeletal response to mechanical loading, growth factors and nutrition are not yet delineated.
There is speculation about the biophysical structure and properties of the sensory and biochemical and molecular biological mechanism of mechano-transduction. When controlled loads of a given magnitude and frequency are applied, in vivo, either in an isolated wing preparation or a rat tibia, bone mineral density is known to increase to an extent which is approximately proportional to the load applied. However, according to the prior art, it is not possible to assess quantitatively the bone-specific regulatory control product and their mechanisms nor to monitor the bone production of local growth factors and cytokines, in these in vivo preparations.
Whilst cell culture preparations do permit an investigator to quantify second messengers, cytokines and local growth factors, they do not permit one to monitor the responses of bone cells to mechanical deformation of the bone matrix which are so important in maintaining and/or remodeling of the skeletal system.
Although growth factors have been shown to enhance the development of new bone, clearly and without the presence of mechanical loading, under these circumstances, the new matrix is not formed along lines of strain and it is that feature, in life, which induces maximum integrity of the new bone so formed. The present authors have been associated with previous work in which the viability of osteoblasts from 2 to 4 week old pigs was successfully maintained, in culture, for 68 days. Careful consideration of these findings led to the hypothesis that, in a suitable novel system, which would permit continuous perfusion and mechanical loading of suitable explanted samples of trabecular bone from mature pigs, viability might be maintained for 10 to 12 days or longer. If this were to be achieved, such a time frame would permit measurements of the rate of bone formation and resorption of the trabecular bone, not available using the systems, apparatus and methods of the prior art. Further, such a novel system would be applicable to the study of human bone.
Up to now, prior art apparatus and systems for investigating bone have either comprised cell culture apparatus of a variety of well-known types or mechanical means for applying three point and four point bending forces to a biological test subject. An example of the three point type is disclosed in U.S. Pat. No. 5,406,853 to Lintilhac and Vesecky and an example of the four point type is disclosed in U.S. Pat. No. 5,383,474 to Recker and Akhter.
The present authors are not aware of any prior art system or apparatus which provides means for simultaneous, contemporaneous and continuous study of axially loaded viable mammalian bone undergoing concurrent continuous perfusion and the effluent medium therefrom.
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